What are the diagnosis and criteria for hepatic encephalopathy?

Diagnosis and Criteria of Hepatic Encephalopathy

Hepatic encephalopathy should be diagnosed clinically when temporal disorientation or asterixis is present in a patient with liver disease, using the West Haven criteria for grading severity from grade II upward, while covert HE (grades 0-1) requires neuropsychological or neurophysiological testing for detection. 1

Classification Framework

HE must be systematically classified according to four essential dimensions 1:

Type Based on Underlying Disease

• Type A: Secondary to acute liver failure 1
• Type B: Due to portosystemic shunt without significant liver disease 1
• Type C: Associated with cirrhosis, with or without portosystemic shunt (most common) 1

Important note: Do not classify HE based on the etiology of the underlying liver disease (e.g., alcohol, viral hepatitis, MAFLD), as this does not impact diagnostic or management approaches 1

Severity Classification

HE exists on a spectrum and is divided into two main categories 1:

Covert HE (West Haven grades 0-1):

• No overt clinical signs or only minimal symptoms 1
• Detectable only through neuropsychological or neurophysiological testing 1
• Includes both minimal HE and grade 1 HE, which overlap significantly due to lack of reference diagnostic methods 1
• Affects more than two-thirds of cirrhotic patients, with prevalence up to 85% 1

Overt HE (West Haven grades 2-4):

• Grade II: Lethargy, temporal disorientation, inappropriate behavior 1
• Grade III: Somnolence, spatial disorientation, marked confusion 1
• Grade IV: Coma 1

Temporal Course

• Episodic: Isolated episodes 1
• Recurrent: Episodes occurring within 6 months or less 1
• Persistent: Continuous behavioral abnormalities with intermittent relapses of overt HE 1

Precipitating Factors

Identify and document whether HE is precipitated or non-precipitated 1. Common precipitating factors include:

• Constipation 1
• Gastrointestinal bleeding 1
• Infections 1
• Hyponatremia 1
• Dehydration/diuretic overdose 1

Diagnostic Approach

Screening Recommendations

Screen all patients with cirrhosis for HE regardless of liver function status, as covert HE is highly prevalent and overt HE carries 1-year and 3-year survival rates of only 42% and 23%, respectively 1

Clinical Diagnosis of Overt HE

The diagnosis is straightforward when specific clinical signs are present 1:

Key clinical features to systematically investigate 1:

• Asterixis (flapping tremor)
• Psychomotor slowing
• Sleep-wake cycle inversion
• Temporal and spatial disorientation
• Impaired consciousness

Grading tools:

• Use West Haven criteria when temporal disorientation is present (grades ≥2) 1
• Add Glasgow Coma Scale for patients with grades III-IV or those in intensive care settings 1

Critical pitfall: The West Haven scale has limited inter-observer reliability for grade I HE, as subtle hypokinesia and psychomotor slowing are easily overlooked 1. However, detection of disorientation and asterixis has good inter-rater reliability 1

Diagnosis of Covert HE

All cirrhotic patients should be screened for covert HE 1. The animal naming test is recommended among available assessments 1.

Additional elements to investigate during neurological examination 1:

• Apraxia
• Dysexecutive syndrome
• Joviality or disinhibition
• Apathy
• Psychomotor retardation

Interview the patient and family members to characterize cognitive changes 1

Mandatory Differential Diagnosis

A comprehensive diagnostic workup is required to exclude other causes of altered mental status 1. The following conditions must be systematically ruled out 1:

Metabolic/Endocrine:

• Diabetic emergencies (hypoglycemia, ketoacidosis, hyperosmolar state, lactic acidosis)
• Hyponatremia and hypercalcemia
• Uremic encephalopathy (can overlap with HE in end-stage liver disease)

Toxic/Pharmacologic:

• Alcohol intoxication, withdrawal, or Wernicke encephalopathy
• Benzodiazepines, neuroleptics, opioids

Infectious/Inflammatory:

• Neuroinfections
• Sepsis (can both cause encephalopathy independently and precipitate HE)

Neurologic:

• Intracranial bleeding and stroke
• Nonconvulsive epilepsy
• Dementia (primary and secondary)
• Brain lesions (traumatic, neoplastic, normal pressure hydrocephalus)

Other:

• Psychiatric disorders
• Obstructive sleep apnea
• Severe medical stress (organ failure, inflammation)

Critical consideration: Hyponatremia and sepsis can produce encephalopathy independently while simultaneously precipitating HE through pathophysiological interactions 1

Clinical Pitfalls and Key Considerations

• Recognition of precipitating factors supports the diagnosis of HE and should be actively sought 1
• The presence of portosystemic shunts facilitates HE occurrence and is associated with more severe forms 1
• Every case of HE should be documented with all four classification dimensions (type, severity, temporal course, precipitating factors) and reassessed at clinically relevant intervals 1
• The term "brain failure" in acute-on-chronic liver failure should be replaced with "acute encephalopathy" and should not be used synonymously with HE, as alternative or concomitant causes may exist 1